Low-Gradient Aortic Stenosis With Preserved LVEF

Study Questions:

What are the mortality implications and what is the survival impact of aortic valve replacement (AVR) among patients with low-gradient (LG) aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF)?


A meta-analysis was performed using studies published between 2005 and 2015 that addressed mortality in patients with LG AS and preserved LVEF, including paradoxical low-flow (i.e., stroke volume index <35 ml/m2) LG (LF-LG) and normal-flow (NF-LG), and those with high-gradient (≥40 mm Hg) AS or moderate AS. The primary outcome was survival benefit associated with AVR. A secondary outcome measure was overall mortality regardless of treatment.


A total of 18 studies were included in the analysis. Patients with LF-LG AS had increased mortality compared with patients with moderate AS (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.31-2.17), NF-LG (HR, 1.80; 95% CI, 1.29-2.51), and high-gradient AS (HR, 1.67; 95% CI, 1.16-2.39) AS. AVR was associated with reduced mortality in patients with LF-LG (HR, 0.44; 95% CI, 0.25-0.77). A similar benefit occurred with AVR in patients with NF-LG (HR, 0.48; 95% CI, 0.28-0.83). Compared to patients with high-gradient AS, those with LF-LG were less likely to be referred to AVR (odds ratio, 0.32; 95% CI, 0.21-0.49).


Patients with paradoxical LF-LG AS and NF-LG AS have increased risk of mortality compared with other subtypes of AS with preserved LVEF, and improved outcome with AVR.


Debate continues regarding the clinical impact of LF-LG AS with preserved LVEF. Clinical confounders include concern that measurement error could incorrectly establish a diagnosis of LF-LG severe AS, and that ‘low-flow’ AS could be incorrectly diagnosed without documentation of LF (stroke volume index <35 ml/m2). Using available literature in a meta-analysis, this study provides further support that patients with true LG severe AS (with either LF or NF) are at increased mortality risk, and have improved outcomes associated with AVR.

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